• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.355-362
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• 2014

We have developed a fully automated high throughput drug screening (HTDS) system based on the microfluidic cell culture array to perform combinational chemotherapy. This system has 64 individually addressable cell culture chambers where the sequential combinatorial concentrations of two different drugs can be generated by two microfluidic diffusive mixers. Each diffusive mixer has two integrated micropumps connected to the media and the drug reservoirs respectively for generating the desired combination without the need for any extra equipment to perfuse the solution such as syringe pumps. The cell array is periodically exposed to the drug combination with the programmed LabVIEW system during a couple of days without extra handling after seeding the cells into the microfluidic device and also, this device does not require the continuous generation of solutions compared to the previous systems. Therefore, the total amount of drug being consumed per experiment is less than a few hundred micro liters in each reservoir. The utility of this system is demonstrated through investigating the viability of the prostate cancer PC3 cell line with the combinational treatments of curcumin and tumor necrosis factor-alpha related apoptosis inducing ligand (TRAIL). Our results suggest that the system can be used for screening and optimizing drug combination with a small amount of reagent for combinatorial chemotherapy against cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.179-189
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• 2019

Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape of lung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensive evidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatment modalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approaches with other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas of active investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosine kinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancer management and keeps expanding its clinical implication. This review will discuss the current position and future role of chemotherapy, and specific consideration for its clinical application in the era of precision medicine.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.475-475
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• 2014

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.128-136
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• 2009

Objective: To investigate a clinical worth of combination therapy of Oriental and conventional cancer treatment focusing on reduction of chemotherapy-induced side effects. Methods: 110 patients treated by Oriental treatment after intravenous or oral chemotherapy were reviewed, from January, 2005 to April, 2008 at the East-West Cancer Center of Dunsan Oriental hospital. Symptoms were investigated by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Version 2.0. Results: 80% patients of 110 patients had at least one symptom among eight main side effects (neutropenia, anorexia, nausea, vomiting, diarrhea, stomatitis, constipation, headache). The presence of those was as follows: nausea 63%, anorexia 61 %, neutropenia 45%, vomiting 28%, constipation 21 %, headache 19%, diarrhea 11 %, and stomatitis 10%. Except neutropenia, above symptoms has ameliorated by Oriental treatment in seven treat days. Conclusions: This study first presented the general characteristics of cancer patients treated by Oriental and conventional therapy, and showed a clinical potential of combinational therapy aiming to chemotherapy-induced side effects.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5353-5361
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• 2012

Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1186-1191
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• 2004

The root of Saussurea lappa includes sesquiterpene lactones such as costunolide and dehydrocostus lactone, and has been shown to be anti-tumorigenic with being used in traditional medicinal therapy in the Eastern Asia. However, the molecular basis of the effects of Saussurea lappa on fate of gastric carcinoma, which incur very frequently in the area, has not been well identified. In this study, the cytostatic effects of Saussurea lappa were examined using gastric AGS cancer cells. Cell viability was dramatically reduced by Saussurea lappa, in a dose-dependent manner. As time passed after its treatment, apoptotic population was increased and clearly showed G2-arrest. Being consistent, its treatment resulted in maintaining of G1 and S-phase cyclins D1, E, and A even until a significant apoptotic population was observed, for example, at 24h after treatment. However, G2/M phase cyclin B1 was reduced even at 12 h after treatment. In addition, its treatment increased expression of p53, p21/sup Wafl / cyclin dependent kinase inhibitor (CKI), and Bax, resulted in cleavages of procaspase 3 and poly ADP-ribose polymerase(PARP), indicating that such G2 arrest- and apoptosis-related molecules are involved. Therefore, these suggest that extracts of Saussurea lappa root may be a safer and effective reagent to deal with gastric cancers either by traditional herbal therapy or combinational therapy with conventional chemotherapy.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.80-89
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• 2022

The targeting of DNA methylation in cancer using DNA hypomethylating drugs has been well known to sensitize cancer cells to chemotherapy and immunotherapy by affecting multiple pathways. Herein, we investigated the combinational effects of DNA hypomethylating drugs and ionizing radiation (IR) in human sarcoma cell lines both in vitro and in vivo. Clonogenic assays were performed to determine the radiosensitizing properties of two DNA hypomethylating drugs on sarcoma cell lines we tested in this study with multiple doses of IR. We analyzed the effects of 5-aza-dC or SGI-110, as DNA hypomethylating drugs, in combination with IR in vitro on the proliferation, apoptosis, caspase-3/7 activity, migration/invasion, and Western blotting using apoptosis- or autophagy-related factors. To confirm the combined effect of DNA hypomethylating drugs and IR in our in vitro experiment, we generated the sarcoma cells in nude mouse xenograft models. Here, we found that the combination of DNA hypomethylating drugs and IR improved anticancer effects by inhibiting cell proliferation and by promoting synergistic cell death that is associated with both apoptosis and autophagy in vitro and in vivo. Our data demonstrated that the combination effects of DNA hypomethylating drugs with radiation exhibited greater cellular effects than the use of a single agent treatment, thus suggesting that the combination of DNA hypomethylating drugs and radiation may become a new radiotherapy to improve therapeutic efficacy for cancer treatment.